Low doses of glyphosate-based herbicide in ewe lambs alter genes involved in follicular development.

ALARCÓN R; DIOGUARDI GH; ALEGRE AL; LOVERA L; MUÑOZ-DE-TORO M; INGARAMO PI; RIVERA OE; LUQUE EH

modalidad virtual

Congreso; - Reunión conjunta de sociedades de biociencias. SAIC- SAI- AAFE- NANOMED.ar. Mar del Plata, 17 ? 20 de noviembre de 2021; 2021

The exposure of ewe lambs to endocrine disruptor compounds may alter female fertility. Previously we demonstrate that glyphosate-based herbicides (GBH) alter ovarian follicular development. Our hypothesis suggests that exposure of ewe lambs during an early postnatal development to GBH may modify the ovarian gene expression even after exposure has ended. The aim of the present study was to compare the effect of oral and subcutaneous GBH exposure from postnatal day (PND) 1 to PND14 on the expression of ovarian genes at PND45. Ewe lambs were exposed to a subcutaneous (n: 5) or an oral (n: 5) low dose of a GBH (glyphosate at 2 mg/Kg/day) and controls (n: 12) to saline solution. On PND45, the ovaries were sectioned and immediately frozen at -80 °C for RNA extraction. Levels of mRNA of genes involved in follicular development such as steroid receptors (ESR1, ESR2 and PR), follicle-stimulating hormone receptor (FSHR), bone morphogenetic protein 15 (BMP15), BMP receptor 1B (BMPR1B), growth and differentiation factor 9 (GDF9), insulin-like growth factor 2 (IGF-2) were evaluated. The mRNA expression of β-Actin protein was used as housekeeping gene. The mRNA expression levels in treated lambs were indicated as values relative to those of control group. Lambs exposed to GBH showed a reduction of FSHR (scGBH=0.45±0.06; oGBH=0.51±0.09) and GDF9 (scGBH=0.54±0.05; oGBH=0.53±0.10). Interestingly, the GBH effects on ovary gene expression were similar in both routes of exposure. No changes were observed in mRNA expression in the other genes assayed (ESR1, ESR2, PR, BMP15, BMPR1B and IGF-2). Our results demonstrated that after the neonatal exposure to low doses of GBH, the expression of two genes involved in ovine follicular development are altered independently of administration route. These results provide mechanistic evidences related the altered follicular development in lambs exposed to GBH and raise concern about ovarian function in adults.